Fanconi syndrome accompanied by renal function decline with tenofovir disoproxil fumarate: a prospective, case-control study of predictors and resolution in HIV-infected patients
The predictors of Fanconi syndrome (FS) accompanied by renal function decline with use of the antiretroviral tenofovir disoproxil fumarate (TDF) have not been assessed. In addition, the natural history of renal recovery from FS after TDF discontinuation is not well-described. We prospectively enroll...
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| Veröffentlicht in: | PloS one 2014-03, Vol.9 (3), p.e92717 |
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| creator | Gupta, Samir K Anderson, Albert M Ebrahimi, Ramin Fralich, Todd Graham, Hiba Scharen-Guivel, Valeska Flaherty, John F Fortin, Claude Kalayjian, Robert C Rachlis, Anita Wyatt, Christina M |
| description | The predictors of Fanconi syndrome (FS) accompanied by renal function decline with use of the antiretroviral tenofovir disoproxil fumarate (TDF) have not been assessed. In addition, the natural history of renal recovery from FS after TDF discontinuation is not well-described.
We prospectively enrolled HIV-infected patients receiving TDF with newly identified FS (defined as at least two markers of proximal tubulopathy and either a >25% decline in creatinine clearance (CrCl) from pre-TDF values or a CrCl 70% of pre-TDF values) although most participants had full normalization of proximal tubulopathy markers within two months of TDF discontinuation.
FS, defined by specific CrCl decreases and markers of tubulopathy, is more likely in those who have received or are currently receiving concomitant lopinavir/ritonavir or who had lower CrCl prior to TDF initiation. Half of those with protocol-defined FS had CrCl recover to near pre-TDF values during the first year after TDF discontinuation. |
| doi_str_mv | 10.1371/journal.pone.0092717 |
| format | Article |
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We prospectively enrolled HIV-infected patients receiving TDF with newly identified FS (defined as at least two markers of proximal tubulopathy and either a >25% decline in creatinine clearance (CrCl) from pre-TDF values or a CrCl <60 mL/min in those without a known pre-TDF CrCl) in a multicenter observational study. These case participants were matched 1:2 to controls; characteristics between the two groups were compared. Case participants with known pre-TDF CrCl values were then followed over 48 weeks to assess renal recovery.
Nineteen cases and 37 controls were enrolled. In multivariable analysis, previous or concurrent use of lopinavir/ritonavir [OR 16.37, 95% CI (2.28, 117.68); P = 0.006] and reduced creatinine clearance prior to initiation of TDF [OR 1.44 for every 5 mL/min reduction, 95% CI (1.09, 1.92); P = 0.012; OR 19.77 for pre-TDF CrCl lower than 83 mL/min, 95% CI (2.24, 174.67); P = 0.007] were significantly associated with FS. Of the 14 cases followed for resolution, 7 (50%) achieved at least partial resolution (defined as recovering CrCl >70% of pre-TDF values) although most participants had full normalization of proximal tubulopathy markers within two months of TDF discontinuation.
FS, defined by specific CrCl decreases and markers of tubulopathy, is more likely in those who have received or are currently receiving concomitant lopinavir/ritonavir or who had lower CrCl prior to TDF initiation. Half of those with protocol-defined FS had CrCl recover to near pre-TDF values during the first year after TDF discontinuation.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0092717</identifier><identifier>PMID: 24651857</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acquired immune deficiency syndrome ; Adenine - adverse effects ; Adenine - analogs & derivatives ; Adenine - therapeutic use ; Adult ; AIDS ; Anti-HIV Agents - adverse effects ; Anti-HIV Agents - therapeutic use ; Antiretroviral agents ; Antiretroviral drugs ; Biology and Life Sciences ; Case-Control Studies ; Control ; Creatinine ; Creatinine - urine ; Fanconi syndrome ; Fanconi Syndrome - complications ; Female ; Glomerular Filtration Rate ; HIV ; HIV infections ; HIV Infections - complications ; HIV Infections - drug therapy ; HIV patients ; Human immunodeficiency virus ; Humans ; Kidney Diseases - chemically induced ; Kidney Diseases - physiopathology ; Kidney Function Tests ; Laboratories ; Lopinavir ; Male ; Markers ; Medical research ; Medicine and health sciences ; Middle Aged ; Multivariable control ; Organophosphonates - adverse effects ; Organophosphonates - therapeutic use ; Patients ; Prognosis ; Prospective Studies ; Recovery ; Renal function ; Research and Analysis Methods ; Risk Factors ; Ritonavir ; Tenofovir</subject><ispartof>PloS one, 2014-03, Vol.9 (3), p.e92717</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Gupta et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Gupta et al 2014 Gupta et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-4362d7816927529afb0919da8ab6d94dab02c7b3358b2d0f34fea3c88ba7ba263</citedby><cites>FETCH-LOGICAL-c692t-4362d7816927529afb0919da8ab6d94dab02c7b3358b2d0f34fea3c88ba7ba263</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3961428/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3961428/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24651857$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Seguro, Antonio Carlos</contributor><creatorcontrib>Gupta, Samir K</creatorcontrib><creatorcontrib>Anderson, Albert M</creatorcontrib><creatorcontrib>Ebrahimi, Ramin</creatorcontrib><creatorcontrib>Fralich, Todd</creatorcontrib><creatorcontrib>Graham, Hiba</creatorcontrib><creatorcontrib>Scharen-Guivel, Valeska</creatorcontrib><creatorcontrib>Flaherty, John F</creatorcontrib><creatorcontrib>Fortin, Claude</creatorcontrib><creatorcontrib>Kalayjian, Robert C</creatorcontrib><creatorcontrib>Rachlis, Anita</creatorcontrib><creatorcontrib>Wyatt, Christina M</creatorcontrib><title>Fanconi syndrome accompanied by renal function decline with tenofovir disoproxil fumarate: a prospective, case-control study of predictors and resolution in HIV-infected patients</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The predictors of Fanconi syndrome (FS) accompanied by renal function decline with use of the antiretroviral tenofovir disoproxil fumarate (TDF) have not been assessed. In addition, the natural history of renal recovery from FS after TDF discontinuation is not well-described.
We prospectively enrolled HIV-infected patients receiving TDF with newly identified FS (defined as at least two markers of proximal tubulopathy and either a >25% decline in creatinine clearance (CrCl) from pre-TDF values or a CrCl <60 mL/min in those without a known pre-TDF CrCl) in a multicenter observational study. These case participants were matched 1:2 to controls; characteristics between the two groups were compared. Case participants with known pre-TDF CrCl values were then followed over 48 weeks to assess renal recovery.
Nineteen cases and 37 controls were enrolled. In multivariable analysis, previous or concurrent use of lopinavir/ritonavir [OR 16.37, 95% CI (2.28, 117.68); P = 0.006] and reduced creatinine clearance prior to initiation of TDF [OR 1.44 for every 5 mL/min reduction, 95% CI (1.09, 1.92); P = 0.012; OR 19.77 for pre-TDF CrCl lower than 83 mL/min, 95% CI (2.24, 174.67); P = 0.007] were significantly associated with FS. Of the 14 cases followed for resolution, 7 (50%) achieved at least partial resolution (defined as recovering CrCl >70% of pre-TDF values) although most participants had full normalization of proximal tubulopathy markers within two months of TDF discontinuation.
FS, defined by specific CrCl decreases and markers of tubulopathy, is more likely in those who have received or are currently receiving concomitant lopinavir/ritonavir or who had lower CrCl prior to TDF initiation. Half of those with protocol-defined FS had CrCl recover to near pre-TDF values during the first year after TDF discontinuation.</description><subject>Acquired immune deficiency syndrome</subject><subject>Adenine - adverse effects</subject><subject>Adenine - analogs & derivatives</subject><subject>Adenine - therapeutic use</subject><subject>Adult</subject><subject>AIDS</subject><subject>Anti-HIV Agents - adverse effects</subject><subject>Anti-HIV Agents - therapeutic use</subject><subject>Antiretroviral agents</subject><subject>Antiretroviral drugs</subject><subject>Biology and Life Sciences</subject><subject>Case-Control Studies</subject><subject>Control</subject><subject>Creatinine</subject><subject>Creatinine - urine</subject><subject>Fanconi syndrome</subject><subject>Fanconi Syndrome - complications</subject><subject>Female</subject><subject>Glomerular Filtration Rate</subject><subject>HIV</subject><subject>HIV infections</subject><subject>HIV Infections - complications</subject><subject>HIV Infections - drug therapy</subject><subject>HIV patients</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Kidney Diseases - chemically induced</subject><subject>Kidney Diseases - physiopathology</subject><subject>Kidney Function Tests</subject><subject>Laboratories</subject><subject>Lopinavir</subject><subject>Male</subject><subject>Markers</subject><subject>Medical research</subject><subject>Medicine and health sciences</subject><subject>Middle Aged</subject><subject>Multivariable control</subject><subject>Organophosphonates - adverse effects</subject><subject>Organophosphonates - therapeutic use</subject><subject>Patients</subject><subject>Prognosis</subject><subject>Prospective Studies</subject><subject>Recovery</subject><subject>Renal function</subject><subject>Research and Analysis Methods</subject><subject>Risk Factors</subject><subject>Ritonavir</subject><subject>Tenofovir</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9-K1DAUxoso7rr6BqIBQRDsmCZt03ohLIvrDiws-Gdvw2mSzmTpJDVJx53X8gnNzHSWKShIL9qc_s53vpzkJMnLDM8yyrIPd3ZwBrpZb42aYVwTlrFHyWlWU5KWBNPHR98nyTPv7zAuaFWWT5MTkpdFVhXsNPl9CUZYo5HfGOnsSiEQwq56MFpJ1GyQU7EIagcjgrYGSSU6bRT6pcMSBWVsa9faIam97Z2911t0BQ6C-ogAxZDvVcxcq_dIgFdprBWc7ZAPg9wg20ZESS2CdR6BkbGct92wK6UNuprfptq0USGa6SFoZYJ_njxpofPqxfg-S35cfv5-cZVe33yZX5xfp6KsSUhzWhLJqiwuWEFqaBtcZ7WECppS1rmEBhPBGkqLqiEStzRvFVBRVQ2wBkhJz5LXe92-s56P7fY8K3BVVxSTKhLzPSEt3PHe6bjzDbeg-S5g3YKDC1p0ikcDsiRQy4JAXhV1A9FE07JW4ozQhkStT2O1oVkpKeJOHXQT0ekfo5d8Ydec1mWW78y8GQWc_TkoH_5heaQWEF3F3tooJlbaC36es4oVJaM4UrO_UPGRaqXjEapWx_gk4d0kYXvM6j4sYPCez799_X_25nbKvj1ilwq6sDxcED8F8z0o4pXzTrUPncsw387LoRt8Oy98nJeY9uq46w9JhwGhfwBtWhWM</recordid><startdate>20140320</startdate><enddate>20140320</enddate><creator>Gupta, Samir K</creator><creator>Anderson, Albert M</creator><creator>Ebrahimi, Ramin</creator><creator>Fralich, Todd</creator><creator>Graham, Hiba</creator><creator>Scharen-Guivel, Valeska</creator><creator>Flaherty, John F</creator><creator>Fortin, Claude</creator><creator>Kalayjian, Robert C</creator><creator>Rachlis, Anita</creator><creator>Wyatt, Christina M</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20140320</creationdate><title>Fanconi syndrome accompanied by renal function decline with tenofovir disoproxil fumarate: a prospective, case-control study of predictors and resolution in HIV-infected patients</title><author>Gupta, Samir K ; Anderson, Albert M ; Ebrahimi, Ramin ; Fralich, Todd ; Graham, Hiba ; Scharen-Guivel, Valeska ; Flaherty, John F ; Fortin, Claude ; Kalayjian, Robert C ; Rachlis, Anita ; Wyatt, Christina M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-4362d7816927529afb0919da8ab6d94dab02c7b3358b2d0f34fea3c88ba7ba263</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Acquired immune deficiency syndrome</topic><topic>Adenine - 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In addition, the natural history of renal recovery from FS after TDF discontinuation is not well-described.
We prospectively enrolled HIV-infected patients receiving TDF with newly identified FS (defined as at least two markers of proximal tubulopathy and either a >25% decline in creatinine clearance (CrCl) from pre-TDF values or a CrCl <60 mL/min in those without a known pre-TDF CrCl) in a multicenter observational study. These case participants were matched 1:2 to controls; characteristics between the two groups were compared. Case participants with known pre-TDF CrCl values were then followed over 48 weeks to assess renal recovery.
Nineteen cases and 37 controls were enrolled. In multivariable analysis, previous or concurrent use of lopinavir/ritonavir [OR 16.37, 95% CI (2.28, 117.68); P = 0.006] and reduced creatinine clearance prior to initiation of TDF [OR 1.44 for every 5 mL/min reduction, 95% CI (1.09, 1.92); P = 0.012; OR 19.77 for pre-TDF CrCl lower than 83 mL/min, 95% CI (2.24, 174.67); P = 0.007] were significantly associated with FS. Of the 14 cases followed for resolution, 7 (50%) achieved at least partial resolution (defined as recovering CrCl >70% of pre-TDF values) although most participants had full normalization of proximal tubulopathy markers within two months of TDF discontinuation.
FS, defined by specific CrCl decreases and markers of tubulopathy, is more likely in those who have received or are currently receiving concomitant lopinavir/ritonavir or who had lower CrCl prior to TDF initiation. Half of those with protocol-defined FS had CrCl recover to near pre-TDF values during the first year after TDF discontinuation.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24651857</pmid><doi>10.1371/journal.pone.0092717</doi><tpages>e92717</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2014-03, Vol.9 (3), p.e92717 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1508983028 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Acquired immune deficiency syndrome Adenine - adverse effects Adenine - analogs & derivatives Adenine - therapeutic use Adult AIDS Anti-HIV Agents - adverse effects Anti-HIV Agents - therapeutic use Antiretroviral agents Antiretroviral drugs Biology and Life Sciences Case-Control Studies Control Creatinine Creatinine - urine Fanconi syndrome Fanconi Syndrome - complications Female Glomerular Filtration Rate HIV HIV infections HIV Infections - complications HIV Infections - drug therapy HIV patients Human immunodeficiency virus Humans Kidney Diseases - chemically induced Kidney Diseases - physiopathology Kidney Function Tests Laboratories Lopinavir Male Markers Medical research Medicine and health sciences Middle Aged Multivariable control Organophosphonates - adverse effects Organophosphonates - therapeutic use Patients Prognosis Prospective Studies Recovery Renal function Research and Analysis Methods Risk Factors Ritonavir Tenofovir |
| title | Fanconi syndrome accompanied by renal function decline with tenofovir disoproxil fumarate: a prospective, case-control study of predictors and resolution in HIV-infected patients |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-21T16%3A54%3A41IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Fanconi%20syndrome%20accompanied%20by%20renal%20function%20decline%20with%20tenofovir%20disoproxil%20fumarate:%20a%20prospective,%20case-control%20study%20of%20predictors%20and%20resolution%20in%20HIV-infected%20patients&rft.jtitle=PloS%20one&rft.au=Gupta,%20Samir%20K&rft.date=2014-03-20&rft.volume=9&rft.issue=3&rft.spage=e92717&rft.pages=e92717-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0092717&rft_dat=%3Cgale_plos_%3EA478756730%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1508983028&rft_id=info:pmid/24651857&rft_galeid=A478756730&rft_doaj_id=oai_doaj_org_article_29ad62a9d52a4859ba6d9bf7fd0123b2&rfr_iscdi=true |